Growth properties of artificial heterogeneous human colon tumors

Two clonal cell lines (designated as clones A and D), originally isolated from the heterogeneous DLD-1 human colon adenocarcinoma, were used to produce xenograft tumors in nude mice. Neoplasms produced from either A or D cells alone were compared to those produced from a range of percentage admixtures of the two subpopulations. Then, Gompertzian growth parameters (initial growth rates, retardation rates) were determined, along with estimation of the final asymptotic volumes. It was found that the growth kinetics of the various artificial heterogeneous tumors could not be predicted from knowledge of the growth parameters of the pure clonal xenograft tumors. Additionally, both pure clonal and artificial heterogeneous tumors were enzymatically disaggregated as a function of time postinjection, and it was found that the admixed tumors became more zonal in composition as time progressed. Further, admixtures of extreme composition (i.e., 9% A plus 91% D or 88% A plus 12% D) remained stable with time, while those of intermediate initial composition (i.e., 50% A plus 50% D) did not. All of these data (growth kinetics, zonality, compositional stability) indicate that the growth properties of heterogeneous tumors are very complex.